Preparation Of Pantoprazole Sodium Enteric-Coated Tablets

Pantoprazole (Pantoprazole, PAZ) is a new generation of proton pump inhibitor (PPI)after omeprazole, lansoprazole has came out. It is sued for peptic ulcer disease, including duodenal ulcer, gastric ulcer, reflux-esophagitis, and zollinger-ellison syndrome, especially for ulcers with bleeding, vomiting or can not eat as well as the refractory ulcer and acute pancreatitis. It can also be used to prevent major operation or serious injury caused by stress ulcer. The purpose of the present study was designed to develop a kind of enteric-coated pellet-type tablets which would improve its bioavailability, and which would be more convenient for patients to use.The HPLC ultraviolet method was developed for determination of pantoprazole sodium content in tablets; the UV method for assay in vitro during the studies about physicochemical properties and the release behavior of pantoprazole sodium. The above methods were accurate, reliable and convenient, can meet various analytical requirements.In the preformulation,the results of stability of pantoprazole sodium in several pH fluids showed that,it was less stable as pH value reduced. If pantoprazole sodium was made into enteric dosage form, it can avoid the instability in gastric juice.In the pharmaceutical research, firstly, the PAZ-Na enteric-coated pellets were prepared by fluid-bed coating method. The formulation of the pellets, producing conditions were investigated as the influencing factors on the powder characters and quality of pellets. The resultant pellets were examined on their shape, size distribution, the bulk density and the release profiles in SGF and SIF. Based on the single-factor tests, the optimal formulation were obtained by orthogonal design tests. The results showed that the enteric-coated pellets which were made by optimal formulation were spherical and smooth, the accumulative release in SGF after 2 hours is 2.64%, the accumulative release in SIF after 1 hours is 86.31%.In order to prepare enteric-coated pellet type tablets, several excipients such as the MCC PHI 02, PVPP, PVP, PEG 6000, Lac and Man were explored. The experimental results showed that the MCC PH102 had excellent compressibility properties, so it was selected as the basic excipient of tablets, further study showed that it is better if we use MCC PH102/PVPP/PEG 6000 at the proportionof 2:1:1 as the tablet excipients. the Pantoprazole Sodium Pellets-type tablets were prepared by direct compression method. The formulation of it was optimized through plasticizers, the level of membrane weight and composition and the proportion of excipients, the size of enteric-coated pellets on drug release behavior. The optimized formulation was: the membrane weight was 55%, plasticizer content was 20%, enteric-coated pellets/ excipients (MCC/PPVP/PEG6000=2:1:1) was 5:5,the enteric-pellets size was 0.4-0.5μm. The enteric-coated tablets release in SGF after 2h is less than 10%,in SIF after 1h,the accumulate release percentage more than 85%. On the basis of optimum region, the result showed that the appearance and the release behavior were within requires. The results of the stability tests showed:the tablets were sensitive to the tempertature,humidity and the light. So, the tablets should be tightly and coolly stored away from light.